Otitis media is the most common illness for which children seek medical care. It has its onset in the first year of life, is often recurrent and chronic, with complications and sequelae that include persistent hearing loss and communication disorders. The University of Minnesota Otitis Media Pathogenesis Research Program was established in 1978 to address the complex pathophysiology of this disease through collaborative research. The long-term goal of the research team, which now includes investigators with expertise in otology, pediatrics, audiology, biochemistry, physiology, epidemiology, pathology, anatomy, pharmacology, and biostatistics, is to provide a rational basis for new treatment and prevention strategies through studies of etiology and pathophysiology. Seven integrated projects are included in this application -- 3 with human subjects exclusively, 1 with animal models exclusively, and 3 with both human subjects and animal models to bridge the interspecies gap. All of the patient populations and animal models are established in the Program. The 7 projects are supported by 8 Core Units, which provide consistency in administration, biostatistics, otopathology, biochemistry, microbiology, immunology, pharmacology, physiology and audiology across the projects. Continuing projects include: (1) a longitudinal study to measure middle ear effusion (MEE), demographic and clinical determinants of middle and inner ear OM sequelae; (2) characterization of ME pathology in the OM continuum, ME epithelial cytokeratin expression and morphologic pathogenesis of mucoid OM; (3) study of OM biochemical characteristics; (4) OM antibiotic pharmacology and efficacy studies; and (5) molecular pathogenesis studies of pneumococcal otitis media. New projects include (1) epidemiologic and laboratory investigation of prenatal and neonatal factors on OM during the first 6 months of life; and (2) a study of genetic OM risk determinants using segregation analysis.